The project's objective is to understand more completely the processes involved in implantation of the blastocyst in the endometrium in non-human primates. Studies focus on cellular interactions of the trophoblast and endometrium, and differentiation of the early postimplantation embryo and trophoblast. In 1994 we examined the roles of constituents during adhesion of trophoblast to uterine epithelium, its penetration through the epithelium and migration through stroma. During investigation of the interaction of trophoblast and uterine epithelium, we found that trophoblast shows a greater affinity for the apical junctional complexes and lateral cell membranes than for the apical cell membrane. This implies that there is more than one type of adhesion molecule involved in adhesion to and penetration into the uterine epithelium, and that adhesion of trophoblast to lateral cell membranes of epithelial cells is greater than the adhesions of these cells to one another. Early implantation stages showed a brief period of massive invasion of the endometrium by cytotrophoblast cells during establishment of the trophoblastic shell. An invasion similar to that demonstrated in vitro by human cytotrophoblast cells occurs briefly in vivo. We determined that the earliest absorptive syncytial trophoblast is sp1-positive, that at the time of formation of the trophoblastic shell both the distal trophoblast cells and the large granular lymphocytes (lgl cells) are NCAM-positive, and that there is considerable morphological variation in cytotrophoblast depending on its position within the trophoblastic shell. During the process of implantation, tropho blast cells undergo sequences of differentiation, determined by the derivation of the cells and their current position and environment. At given times in implantation, only some of the responses can be elicited, due to restricted trophoblast populations present. The pleomorphism of trophoblast enables it to respond differently to a variety of maternal conditions encountered. Some early stages appear to have a programmed developmental sequence. Others, such as the invasiveness of cytotrophoblast (extravillous cytotrophoblast), appear to be variable depending on local signals. Finding there is only a brief stage of rapid invasion of cytotrophoblast in the macaque indicates that for most of gestation the invasive potential of cytotrophoblast is inhibited.